Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Antipyretics

Analgesics

Anti-Infective Agents

Dermatologic Agents

Neuroprotective Agents

Anti-Allergic Agents

Central Nervous System Depressants

Amino Acids

Tacrolimus

Dexamethasone

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Cyclophosphamide

Acetaminophen

Melphalan

Cyclosporine

Cyclosporins

Prednisolone

Lenograstim

Mycophenolic Acid

Thymoglobulin

Dexamethasone acetate

BB 1101

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Diphenhydramine

Promethazine

Mechlorethamine

Antilymphocyte Serum

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Adjuvants, Immunologic

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Calcineurin Inhibitors

Analgesics, Non-Narcotic

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Hormonal

Phenylalanine

Study treatment is a high-dose sequential chemotherapy approach to hematopoietic stem cell (HSC) transplant that uses an autologous peripheral blood stem cell (auto-PBSC) transplant followed by allogeneic peripheral blood stem cell (allo-PBSC) transplant to evaluate improved graft vs host disease (GvHD) control. Participant auto-PBSC are mobilized with cyclophosphamide (also to provide cytoreduction) and filgrastim, followed by melphalan as an auto-PBSC conditioning agent, then auto-PBSC infusion. For the allo-PBSC transplant, donors are mobilized with filgrastim, and participants receive a regimen of total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG), followed by infusion of donor allo-PBSC. Solumedrol, diphenhydramine, acetaminophen, and hydrocortisone are administered as premedications, and rabbit anti-thymocyte globulin (ATG) plus mycophenolate mofetil (MMF) are administered for post-allo-PBSC immunosuppression.

Auto-PBSC ≥ 2 to 3 x 10e6 CD34+ cells/kg are intravenously (IV) infused as part of the combination stem cell therapy.

and allogeneic stem cells are administered intravenous (IV) infusion to reestablish hematopoietic function in patients whose bone marrow or immune system is damaged or defective

Autologous peripheral blood stem cells (auto-PBSC) transplantation

Allo-PBSC (target collection ≥ 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy.

Allogeneic peripheral blood stem cells (allo-PBSC) transplantation

Filgrastim is administered subcutaneously (SC) at 10 µg/kg/day for auto-PBSC mobilization starting day 2 of mobilization until the last day of apheresis.

Filgrastim is administered SC at 5 µg/kg/day from Day 6 after auto-PBSC infusion to hematologic recovery.

Filgrastim is administered SC at 16 µg/kg/day for donor allo-PBSC mobilization at from Day - 4 to Day 0, prior to allo-PBSC collection.

Filgrastim

Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.

Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.

Cyclosporine is administered by mouth (PO) for allo-PBSC graft vs host disease (GvHD) prophylaxis at 5 mg/kg from Day -3 through Bay +56. Tacrolimus may substituted.

Total lymphoid irradiation is administered at 80 centigrey (cGy) on Day -11 to -7; and Day -4 to -2 before alllo-PBSC infusion. TLI is also administered at 80 centigrey (cGy) x 2 on Day -1 before alllo-PBSC infusion.

Total lymphoid irradiation

ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion.

Rabbit anti-thymocyte globulin

MMF is administered at 15 mg/kg 3x/day by mouth (PO) after allo-PBSC through Day 40, followed by 10% dose reduction weekly (dose taper) through day 96, and adjusted if there is evidence of MMF-related GI toxicity or excessive myelosuppression

Mycophenolate Mofetil 250mg

Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion

Solumedrol

Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions.

Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions.

Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.

Wen-Kai Weng

To evaluate the toxicity and tolerability of this tandem autologous/allogeneic transplant approach for patients with advanced stage multiple myeloma.

Development of cell-based immunotherapy from allogeneic hematopoietic cell transplantation (HCT) is dependent upon stable T-cell engraftment and the success of this therapeutic approach is likely to be greatest when directed against a minimal rather than gross tumor burden. To this end, tandem transplants with high dose therapy and autologous hematopoietic cell transplantation (AHCT) for tumor cytoreduction followed by non-myeloablative allotransplant have been conducted. In myeloma, this tandem approach results in greater efficacy compared to conventional AHCT.

Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG

A Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) in Multiple Myeloma Patients

To evaluate the incidence acute GvHD of this tandem autologous/allogeneic transplant setting

Engraftment is assessed as:

* Neutrophil engraftment is \> 0.5 x 10⁹/L after cytopenia
* Platelet engraftment is \> 20 x 10⁹/L after cytopenia

Overall response rate (ORR) = Complete Response Rate (CRR) + Partial Response Rate (PRR)

Complete response rate (CRR) was assessed as all of:

* Negative immunoflixation on the serum and urine
* Disappearance of any soft tissue plasmacytomas
* \< 5% plasma cells in bone marrow

Partial response rate (PRR) was assessed as

* \> 50% reduction in serum M-protein plus urine M-protein reduction by 90% or \< 200 mg/24 hr
* If serum M-protein is not measurable, then \> 50% reduction in the involved serum free light chain
* If involved serum free light chain is not measurable, then \> 50% reduction in the bone marrow plasma cell percentage + \> 50% reduction in the size of any soft tissue plasmacytoma.

To evaluate the graft versus myeloma effect by monitoring rate of event-free survival (EFS)

To evaluate the graft versus myeloma effect by monitoring rate of overall survival (OS)

Stanford University

Assistant Professor of Medicine (Blood and Marrow Transplantation)

A high-dose sequential chemotherapy approach with cyclophosphamide and etoposide followed by granulocyte colony stimulating factor (G-CSF) for collection of peripheral blood progenitor cells as well as for cytoreduction. Total Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).The preparatory regimens use BCNU and melphalan.

Autologous-Allogeneic Hematopoietic Stem Cell Transplant

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Wen-Kai Weng, MD; Associate Professor of Medicine

Due to the significance of the allo-PBSC transplant as a component to the treatment plan, participants who did not receive allo-PBSC are not included.

Incidence of Graft Versus Host Disease (GvHD)

Neutrophil Engraftment

Platelet Engraftment

Median Time to Engraftment After Auto-PBSC Transplant

Due to the less intensive conditioning before allo-PBSC, only 2 participants experienced cytopenia, and thus only 2 participants could be evaluated for engraftment after allo-PBSC.

Spots Global Cancer Trial Database for Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial